Synthesis of novel guttiferone E and xanthochymol derivatives with cytotoxicities by inducing cell apoptosis and arresting the cell cycle phase

	Synthesis of novel guttiferone E and xanthochymol derivatives with cytotoxicities by inducing cell apoptosis and arresting the cell cycle phase
	Lin, Xin 1,2,3; Tian, Dongsong 1,2; Fu, Yanhui5 ; Li, Yanan 1,2; Huang, Liejun 1,2; Gu, Wei1,2 ; Song, Jialei 1,2; Li, Yanmei 1,2; Ben-David, Yaacov 1,2; Wen, Min 1,2,3; Yuan, Chunmao 1,2; Hao, Xiaojiang1,2,4
	2019-01-15
发表期刊	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN	0223-5234
卷号	162 页码:765-780
摘要	The mixture of GX (guttiferone E and xanthochymol), an inseparable polycyclic polyprenylated acylphloroglucinol (PPAP), showed moderate cytotoxic activities. The chemical transformation of GX yielded three different types of PPAPs (1, 2, and 3/4). A series of analogs were prepared, and the structures of the 40 newly synthesized compounds were elucidated by 1D and 2D NMR and HR-ESI-MS. The derivatives were screened in vitro for antiproliferative activity against five human cancer cell lines: human leukemic cell lines (HEL and K562), cervical cancer cell line (Hela), human breast adenocarcinoma cell line (MCF-7), and human non-small cell lung cancer cell line (A549), using the MTT assay, and most of the derivatives showed good cytotoxic activities. Noticeably, compound 2, a novel tautomer with a hemiketal, exhibited selective cytotoxic activities against HEL (IC50 = 4.79 +/- 0.23 mu M) and K562 (IC50 = 7.69 +/- 0.34 mu M) leukemia cells. The mechanism studies indicated that compound 2 induced apoptosis and arrested the cell cycle at the G0/G1 phase in the HEL cell line. Furthermore, compound 2 activated the intrinsic pathway by reducing the expression of anti-apoptotic protein Bcl-2 and cell cycle-specific cyclin D1 and by enhancing the pro-apoptotic protein Bax. Moreover, the caspase-3 and PPRP1 levels were also upregulated. Our present results suggest that compound 2 is a potential candidate for developing novel anti-leukemia agents in the future. (C) 2018 Elsevier Masson SAS. All rights reserved.
关键词	Polycyclic polyprenylated acylphloroglucinol Chemical transformation Cytotoxicity Cell apoptosis Cell cycle arrest
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/64193
专题	植物化学与西部植物资源持续利用国家重点实验室
通讯作者	Wen, Min; Yuan, Chunmao; Hao, Xiaojiang
作者单位	1.Guizhou Med Univ, State Key Lab Funct & Applicat Med Plants, Guiyang 550014, Guizhou, Peoples R China 2.Chinese Acad Sci, Key Lab Chem Nat Prod Guizhou Prov, Guiyang 550014, Guizhou, Peoples R China 3.Guizhou Med Univ, Coll Basic Med, Guiyang 550004, Guizhou, Peoples R China 4.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 5.Hainan Normal Univ, Minist Educ, Key Lab Trop Med Plant Chem, Haikou 571158, Hainan, Peoples R China
推荐引用方式 GB/T 7714	Lin, Xin,Tian, Dongsong,Fu, Yanhui,et al. Synthesis of novel guttiferone E and xanthochymol derivatives with cytotoxicities by inducing cell apoptosis and arresting the cell cycle phase[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2019,162:765-780.
APA	Lin, Xin.,Tian, Dongsong.,Fu, Yanhui.,Li, Yanan.,Huang, Liejun.,...&Hao, Xiaojiang.(2019).Synthesis of novel guttiferone E and xanthochymol derivatives with cytotoxicities by inducing cell apoptosis and arresting the cell cycle phase.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,162,765-780.
MLA	Lin, Xin,et al."Synthesis of novel guttiferone E and xanthochymol derivatives with cytotoxicities by inducing cell apoptosis and arresting the cell cycle phase".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 162(2019):765-780.

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